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Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology
Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M et al.. Neuron, 2004-11-01
Topic: Brain proteins, microglia and lab models
We have previously linked families with autosomal-dominant, late-onset parkinsonism to chromosome 12p11.2-q13.1 (PARK8). By high-resolution recombination mapping and candidate gene sequencing in 46 families, we have found six disease-segregating mutations (five missense and one putative splice site mutation) in a gene encoding a large, multifunctional protein, LRRK2 (leucine-rich repeat kinase 2). It belongs to the ROCO protein family and includes a protein kinase domain of the MAPKKK class and several other major functional domains. Within affected carriers of families A and D, six post mortem diagnoses reveal brainstem dopaminergic degeneration accompanied by strikingly diverse pathologies. These include abnormalities consistent with Lewy body Parkinson's disease, diffuse Lewy body disease, nigral degeneration without distinctive histopathology, and progressive supranuclear palsy-like pathology. Clinical diagnoses of Parkinsonism with dementia or amyotrophy or both, with their associated pathologies, are also noted. Hence, LRRK2 may be central to the pathogenesis of several major neurodegenerative disorders associated with parkinsonism.
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APA 7th
Zimprich, A., Biskup, S., Leitner, P., Lichtner, P., Farrer, M., Lincoln, S., et al. (2004). Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. https://doi.org/10.1016/j.neuron.2004.11.005
Vancouver
Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004. doi:10.1016/j.neuron.2004.11.005. PMID: 15541309.
BibTeX
@article{zimprich2004-15541309,
author = {Zimprich, A. and Biskup, S. and Leitner, P. and Lichtner, P. and Farrer, M. and Lincoln, S. and Kachergus, J. and Hulihan, M. and others},
title = {{Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology}},
journal = {Neuron},
year = {2004},
doi = {10.1016/j.neuron.2004.11.005},
pmid = {15541309},
url = {https://doi.org/10.1016/j.neuron.2004.11.005}
}
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Key findings
- Hence, LRRK2 may be central to the pathogenesis of several major neurodegenerative disorders associated with parkinsonism.
Why it matters
This genetic study found six disease-segregating mutations in LRRK2 in families with autosomal-dominant, late-onset parkinsonism, with diverse brain pathologies at post mortem. It concerns parkinsonism and related disorders, not the treatment, cure or prevention of Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 57/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuron) |
| Journal's citation record | 4 / 4 | Neuron: journal h-index 689 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2004 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 3,011 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 125.5 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 6 / 6 | Cited 90.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 20 other studies in this library |
| Still being cited | 4 / 4 | Cited 308 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Thomas Gasser: h-index 136 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of British Columbia: institution h-index 1,424 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15541309) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
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